. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):403-9. PubMed.

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  1. A very interesting view point!

  2. This hypothesis stands also for APP.

  3. Very interesting review providing a fair and original account of the available data. I strongly recommend this paper.

    I would like to remark that the clinical data linking presenilin mutations with non-amyloid dementias have not yet been corroborated with further work demonstrating a causal relationship. For instance, the dementia in the family with the Psen1 insR352 is likely caused by a mutation in progranulin, as reported recently by Boeve et al. (2006).

    References:

    . Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation in progranulin: a clinicopathologic study. Brain. 2006 Nov;129(Pt 11):3103-14. PubMed.

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